What are the guidelines for antiplatelet and fibrinolytic therapy?

From the Guidelines

Aspirin is the cornerstone treatment for antiplatelet therapy, and dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor is recommended after acute coronary syndromes or stent placement, usually for 6-12 months depending on bleeding risk and stent type. For patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), the guidelines recommend aspirin at a dose of 162-325 mg promptly after presentation, and a maintenance dose of 81-325 mg daily continued indefinitely 1. Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor, such as clopidogrel, ticagrelor, or prasugrel, is recommended in addition to aspirin for up to 12 months for patients treated initially with either an early invasive or initial ischemia-guided strategy 1. The choice of P2Y12 inhibitor depends on the patient's risk factors and bleeding risk, with ticagrelor preferred over clopidogrel for patients treated with an early invasive or ischemia-guided strategy 1. For fibrinolytic therapy, IV fibrinolytic treatment is not recommended in patients with NSTE-ACS 1. In patients with ischemic stroke or transient ischemic attack, antiplatelet therapy with aspirin, clopidogrel, or the combination of aspirin and extended-release dipyridamole is recommended for secondary prevention 1. The European guidelines also recommend dual antiplatelet therapy with a P2Y12 inhibitor added to aspirin for 12 months after acute coronary syndromes, unless contraindicated due to excessive risk of bleeding 1. Key considerations when initiating antiplatelet and fibrinolytic therapy include:

• Assessing bleeding risk and recent surgeries
• Monitoring for bleeding complications
• Adjusting therapy based on individual patient factors, including age, weight, renal function, and concomitant medications
• Selecting an antiplatelet regimen based on patient risk factor profiles, cost, tolerance, and other clinical characteristics. Overall, the goal of antiplatelet and fibrinolytic therapy is to reduce the risk of thrombotic events and improve outcomes in patients with cardiovascular disease.

From the FDA Drug Label

PRASUGREL tablets, for oral use Initial U. S. Approval: 2009 WARNING: BLEEDING RISK Prasugrel can cause significant, sometimes fatal, bleeding (5.1,5.2,6.1). Do not use prasugrel in patients with active pathological bleeding or a history of transient ischemic attack or stroke (4.1,4. 2). In patients ≥75 years of age, prasugrel is generally not recommended, except in high-risk patients (diabetes or prior myocardial infarction [MI]), where its use may be considered (8.5). DOSAGE AND ADMINISTRATION Initiate treatment with a single 60 mg oral loading dose (2). Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients <60 kg (2). Patients should also take aspirin (75 mg to 325 mg) daily (2).

The guidelines for antiplatelet and fibrinolytic therapy with prasugrel are as follows:

• Initiation of treatment: A single 60 mg oral loading dose, followed by 10 mg once daily.
• Aspirin use: Patients should also take aspirin (75 mg to 325 mg) daily.
• Contraindications: Active pathological bleeding, prior transient ischemic attack or stroke, and hypersensitivity to prasugrel or any component of the product.
• Special considerations:
  • Patients ≥75 years of age: generally not recommended, except in high-risk patients.
  • Patients <60 kg: consider 5 mg once daily.
  • Patients undergoing CABG: discontinue prasugrel at least 7 days prior to surgery, if possible.
  • Patients with bleeding risk factors: monitor closely and manage bleeding without discontinuing prasugrel, if possible 2.

From the Research

Guidelines for Antiplatelet Therapy

• Dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor, is recommended for patients with acute coronary syndrome (ACS) to reduce cardiovascular event rates 3.
• The choice of P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and duration of DAPT should be based on patient characteristics, including risk of bleeding and myocardial ischemia 3, 4.
• For patients with a low risk of bleeding, prolonged DAPT may be considered, although the optimal duration is not well established 3.
• For patients with a high risk of bleeding, a shorter duration of DAPT (3-6 months) may be reasonable 3.

P2Y12 Inhibitors

• Prasugrel and ticagrelor are more potent than clopidogrel, with a faster onset of action and higher efficacy in reducing ischemic events 3, 5.
• However, prasugrel is associated with an increased risk of bleeding, particularly in patients with a history of stroke or transient ischemic attack 3, 5.
• Ticagrelor has been shown to have a better net efficacy and safety profile compared to prasugrel and clopidogrel 5.

Duration and Discontinuation of DAPT

• Recent trials suggest that discontinuing aspirin rather than the P2Y12 inhibitor may be associated with better outcomes 3.
• The optimal duration of DAPT is not well established, but it is generally recommended for at least 12 months after ACS 3.
• Switching between P2Y12 inhibitors may be necessary in some cases, and the choice of switching strategy should be based on patient characteristics and the specific inhibitors being used 4.

Special Considerations

• Patients with a high risk of bleeding, such as those with a history of bleeding or taking oral anticoagulants, may require a shorter duration of DAPT or a different P2Y12 inhibitor 3.
• Patients with minor stroke or high-risk transient ischemic attack may benefit from DAPT with aspirin and a P2Y12 inhibitor, but this should be balanced against the increased risk of bleeding 6.